LAUSR

Dear Editor: We would to address several challenges that have arisen from the study by Chatziralli et al. [1], which can be specifically summarized below. Several relevant data are missing from the study (Table 1). In the assessment of the final results of this study, we considered the current assertion that evaluation of outcomes has to be guided by anatomical measure data with visual changes as a secondary guide [2]. Accordingly, the final outcomes of this series were unsatisfactory. Specifically, despite a significant mean gain in best-corrected visual acuity (BCVA) of 7.9 and 7.4 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, in patients receiving ranibizumab (Lucentis; Novartis, Basel, Switzerland) and aflibercept (Eylea; Bayer HealthCare, Leverkusen, Germany), respectively, the central subfield thickness (CST) decreased significantly to 340.8 and 364.9 μm, respectively, with both values being more than the cutoff for the upper level of normal CST [3]. Moreover, 8.8% and 7.2% of patients, respectively, needed panretinal photocoagulation. Persistence of these high values of unresolved macular edema indicates that the disease process is still active and progressive, requiring further treatment with antiangiogenic agents. The authors documented that the two treatment arms did not differ significantly with regard to the improvement in BCVA or reduction in CST; and yet, the following findings indicated that there were evidently better final results in the ranibizumab group relative to those in the aflibercept group, namely, the proportions of patients who had BCVA ≥6/12 (35.3% and 32.1%, respectively) and those who gained ≥10 ETDRS letters (50% and 42.9%, respectively) or ≥15 ETDRS letters (35.3% and 32.1%, respectively); the BCVA score (64.8 and 62.7 ETDRS letters, respectively), and the proportion of patients with unresolved macular edema (50% and 57.1%, respectively). These findings are somewhat paradoxical because aflibercept has well-known presumed pharmacological advantages over ranibizumab [4]. Unlike ranibizumab, which does not impair choroidal thickness, aflibercept may result in a significant subfoveal choroidal thickness thinning [5] by suppression of choroidal hyperpermeability and the vasoconstriction. Of note, the prolonged inhibition of vascular endothelial growth factor (VEGF) using aflibercept may affect the integrity of the choriocapillaris considering the key role played by the VEGF-A in the regulation of the survival and permeability of the choriocapillaris. In addition, through the fragment cristalizable (Fc) domain, aflibercept can bind to the Fc receptor of both choriocapillaris endothelial cells and red blood cells, leading to complement mediated cell death [6]. Thus, the choroidal vascular impairment may affect the integrity of the retinal pigment epithelium and the outer retina because the choroid is involved in maintaining perfusion of the outer retinal layers and is the sole source of metabolic exchange for the fovea. The comparison of the final results of this series with those of the Cruise [7], Copernicus [8], and Galileo [9] studies seems to be inappropriate because these pivotal studies included patients with much lower proportions of nonperfused retinal status (e.g., 1.5, 14.9, and 6.8%, respectively) than those of the present study (e.g., 23.5 and 25% in the ranibizumab and aflibercept groups, respectively). * Mihai Călugăru [email protected]